Risk and mechanism of hepatic lipid metabolism disorders induced by subchronic exposure to fipronil in mice
LIU Guang-nan1,2, GUO Ya-jie3, HUANG Su-li2, CHEN Ying2, HU Xiao-xiao2, ZHONG Dan-rong2, TANG Zhi4, KE Yue-bin2, ZENG Huai-cai1,5, LYU Zi-quan2
1. School of Public Health, University of South China, Hengyang, Hunan 421000, China; 2. Shenzhen Municipal Center for Disease Control and Prevention, Shenzhen, Guangdong 518055, China; 3. The Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong 518033, China; 4. School of Public Health, Guangdong Medical University, Dongguan, Guangdong 523808, China; 5. School of Public Health, Guilin Medical University, Guilin, Guangxi 541000, China
Abstract：Objective To study the effects and molecular mechanisms of subchronic exposure to fipronil (FPN) on the homeostasis of hepatic lipid metabolism in adult male mice under different nutritional conditions. Methods C57BL/6J male mice were randomly divided into 8 groups, each group consisting of 7 mice. 4 groups were fed with a normal-chow diet (ND), while other 4 groups with a high-fat diet (HFD). ND-fed and HFD-fed mice were subgrouped by FPN dosage respectively, including the control group and FPN groups of 0.25 mg/kg, 1 mg/kg and 4 mg/kg. They experienced daily oral gavage, and were sacrificed after 5 weeks of exposure to FPN. Body weight and liver weight were measured, and the liver coefficient was calculated. HE staining was performed to observe hepatic morphological changes. The levels of triglycerides (TG), total cholesterol (TC) and free fatty acids (FFA) were detected by biochemical analysis methods. Western Blot and qPCR were used to determine protein and gene expression related to liver lipid metabolism. Results No obvious alterations in body weight and liver weight were observed in ND-fed or HFD-fed mice after FPN treatment. As for ND-fed mice, no significant hepatic pathological changes were found by HE staining, and serum level of TG increased (P<0.05). Hepatic TG and TC levels increased in 0.25 mg/kg FPN group (P<0.05), but decreased in 4 mg/kg FPN group (P<0.05). Hepatic FFA level declined (P<0.05). PPARα protein expression increased (P<0.05). Acc protein expression increased in 0.25 mg/kg FPN group (P<0.05), but was down-regulated in 4 mg/kg FPN group (P<0.05). As for HFD-fed mice, HE staining revealed that there were significant pathological changes in liver tissue with accumulated lipid deposition. Serum TG and TC levels decreased (P<0.05), while hepatic TG, TC and FFA levels increased (P<0.05). PPARα protein expression decreased with the increasing dosage of FPN (P<0.05), but Acc and Srebp-1c proteinexpression decreased (P<0.05). Conclusion Subchronic exposure to FPN can disturb the homeostasis of hepatic lipid metabolism in ND-fed mice, which may further initiate the development of nonalcoholic fatty liver disease (NAFLD), especially in exposure to low doses of FPN. Under HFD-fed condition, exposure to FPN induces obvious hepatic pathological changes in mice. And there is a dose-response relationship between FPN exposure level and the risk to develop abnormal hepatic lipid accumulation and even NAFLD.
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2022, Vol. 29 
